DDIT4
The DDIT4 (RTP801, REDD1) gene was first reported by the assignee of the instant application. U.S. Pat. Nos. 6,455,674, 6,555,667, and 6,740,738, and related patents to the assignee of the instant application and hereby incorporated by reference in their entirety, disclose the RTP801 polynucleotide and polypeptide, and antibodies directed toward the polypeptide. RTP801 represents a unique gene target for hypoxia-inducible factor-1 (HIF-1) that may regulate hypoxia-induced pathogenesis independently of growth factors such as VEGF. Double stranded RNA molecules, which down regulate DDIT4 are disclosed in, inter alia, U.S. Pat. Nos. 7,741,299; 8,067,570; 7,872,119 and US Patent Publication No. 2011/0028531, to the Assignee of the present application and hereby incorporated by reference in their entirety. Additional molecules are disclosed in U.S. Pat. No. 7,655,788 and US Patent Publication No 2010/0285038.
US Application Publication Nos 2010/0292301 and 2011/0112168, and PCT Patent Publication Nos. WO 2011/066475, WO 2011/084193, WO 2011/085056 and WO 2012/078536 to the assignee of the present application and hereby incorporated by reference in their entirety, disclose nucleic acid sequences and modifications useful in generating dsRNA molecules.
US Application Publication Nos. 2011/0142917, 2011/0229557 and 2012/0141378 to the assignee of the present application and hereby incorporated by reference in their entirety, disclose compositions and methods of use comprising DDIT4 dsRNA.
A patent application disclosing phenyl hydrocarbyl moieties useful for covalently attaching to dsRNA, to the assignee of the present application, is filed concomitantly with the present application.
Molecules, compositions, methods and kits useful for the down regulation of DDIT4 and which exhibit at least one of increased bioavailability, improved biodistribution, increased serum circulation time, increased serum stability, decreased serum clearance, improved cellular uptake, reduced off target activity, reduced immunogenicity, improved endosomal release, improved specific delivery to target tissue or cell and increased knock down activity when compared to unmodified dsRNA counterparts are needed.